Abstract To address the concern that few hematopoietic cell transplant (HCT) patients, especially allogeneic HCT patients, enter clinical trials to explore strategies to improve outcomes, the NHLBI and NCI chartered the Blood and Marrow Clinical Trials Network (BMT CTN) in 2001. Aim 1of this application proposes continuation of participation of the UF Consortium, consisting of the University of Florida (UF) and Emory University (EU), as a core consortium of the BMT CTN for continued participation in multiple ongoing trials and trials to be implemented in the next funding cycle. The UF Consortium performs >600 HCTs annually. The UF Consortium has been a highly effective core center since the BMT CTN's inception in 2001 with a proven track record of consistently meeting or exceeding all annual BMT CTN performance standards. The UF Consortium has participated in 41 of 42 BMT CTN trials, has consistently exceeded annual target enrollments, has been in the top 25% of core centers/consortia in enrollment during the current funding cycle, and has doubled its enrollments to BMT CTN trials during the past funding cycle. Drs. Wingard and Waller and other UF consortium investigators have provided strong scientific leadership, authoring 25 publications (4 as first author and 3 as senior author), serving on 14 Protocol Committees (2 as PI), 6 Endpoint Review Committees, and 7 Administrative and Technical Committees (serving as chair of 3). Both have served in leadership roles in the NIH State of Science Symposia. Data reporting error rates have been well below the targeted error rate for the BMT CTN studies (2.0 % or lower). Similarly, timeliness of reports has exceeded CTN acceptance standards. The advantage of the UF Consortium is that this core will be able to continue to expand its accrual to BMT CTN trials. Unique strengths the UF Consortium brings to this next cycle of funding is access to large numbers of Sickle Cell Disease (SCD) patients, robust interactions of each HCT team with SCD collaborators, an experienced immune reconstitution laboratory, dendritic cell manufacturing and other novel cell therapy manufacturing capacity at both sites with multiple ongoing cell vaccine/HCT trials at both sites. Aim 2 of this application proposes a protocol concept to address 2 high priority research topics identified in the States of Science Symposia: graft versus host disease (GVHD) and infection. Alterations in the diversity of the gut microbiota after allogeneic HCT are associated with risks for serious infections, GVHD, treatment- related mortality, pulmonary complications and relapse. Indole compounds, produced by the intestinal microbiota, have immunoregulatory properties. Pilot murine studies by us indicate the ability of an indole prebiotic to reduce the risk for GVHD while preserving graft versus leukemia effects. In this application we propose to test an indole prebiotic intervention to prevent GVHD and serious infection, first in a randomized phase 2 trial to assess feasibility in a multicenter setting, then in a phase 3 randomized trial. This novel approach to prevent GVHD offers the prospect to avoid toxicities of current immunosuppressive regimens.